This project studies the interaction of dynorphin A with morphine in chronic pain patients. The long term aim is to provide a therapy which enhances the analgesic properties of opioids in opioid-tolerant patients who are not receiving adequate pain relief. In animal experiments, concurrent administration of dynorphin A(1-13) has been shown to potentiate morphine-induced analgesia in rodents tolerant to morphine and to suppress the expression of withdrawal. Preliminary studies in opioid-medicated patients have shown that dynorphin can be administered safely and enhance pain relief. This project is a pilot study to evaluate the ability of dynorphin A (1- 13) to enhance the analgesic effect of morphine (or hydromorphone) in patients requiring relatively high doses of these opioids. Results from three treatment groups will be compared: 1) a single dose of an established opioid dose, 2) a single dose of 50% of an established opioid dose and a low dose of dynorphin A, and 3) a single dose of 50% of an established opioid dose and a high dose of dynorphin A. Patients will self-assess pain intensity, pain relief, and mood prior to, and at designated intervals after medication. The study will be conducted by an experienced pain research group at Memorial Sloan-Kettering Cancer Center under an existing NTI-sponsored IND.